F-652 (recombinant human interleukin-22) for treatment of schizophrenia and psychosis

Abstract

Microbial translocation (MT) is implicated in schizophrenia and other psychotic disorders, by allowing toxins and microorganisms to penetrate the intestinal barrier and enter the systematic circulation, wherein such toxins and microorganisms may be a causal agent for schizophrenia or psychosis. IL-22 has been shown to have protective effects in the gut and preventing lipopolysaccharide (LPS) migration into host tissues and preventing MT. Compositions and formulations of IL-22 and related chemical derivatives are disclosed as treatments for schizophrenia and other psychotic disorders. A form of IL-22 that may be useful is F-652, a dimer of IL-22 having superior pharmaceutic properties than native IL-22.

1 . A method of treating schizophrenia or psychosis, comprising the administration of a pharmaceutical formulation containing and active agent comprising IL-22 or a dimer, fusion protein or conjugate thereof to a person suffering from schizophrenia. 
     
     
         2 . The method of treating schizophrenia or psychosis of  claim 1  wherein the active agent is interleukin-22 having the sequence of SEQ ID NO: 1 (179 amino acid sequence of IL-22) or F-652 having SEQ ID NO: 2. 
     
     
         3 . The method of  claim 1  wherein the active agent is F-652. 
     
     
         4 . The method of  claim 1 , wherein the active agent is administered in an injectable formulation containing at least one excipient selected from a bulking agent, a buffering agent, a antimicrobial preservative, a chelating agent, an antioxidant, a reducing agent, a solvent, and a cosolvent, or a combination thereof. 
     
     
         5 . The method of  claim 4 , wherein the injection is administered subcutaneously, by intramuscular injection or intravenously. 
     
     
         6 . The method of  claim 1  wherein the dose of the active agent is 1.0 μg/kg of body weight to 200 μg/kg of body weight. 
     
     
         7 . The method of  claim 6 , wherein the dose of the active agent is 5.0 μg/kg of body weight to 100 μg/kg of body weight or 25 μg/kg of body weight to 75 μg/kg of body weight or 45 μg/kg of body weight. 
     
     
         8 . The method of  claim 6 , wherein the dose of the active agent is administered once per day, two times per week, once per week, once every 14 days, once every 21 days, or once per month. 
     
     
         9 . The method of treating schizophrenia or psychosis of  claim 1  wherein the active agent inhibits microbial translocation in the intestines. 
     
     
         10 . The use of F-652 for the treatment of schizophrenia or psychosis. 
     
     
         11 . A pharmaceutical composition for the treatment of schizophrenia or psychosis, wherein the composition comprises an interleukin-22 agonist. 
     
     
         12 . The pharmaceutical composition of  claim 11 , wherein the interleukin-22 agonist is F-652.